Nematocin, a C. elegans oxytocin-like peptide, links reproductive decline to intestinal lipid metabolism

Oxytocin and vasopressin are well-known for their roles in reproduction, but their influence on peripheral lipid metabolism is a more recent discovery. The intricate connection between these signaling systems and how reproductive capacity declines with age remains largely unexplored. Understanding this link is crucial, as reproductive aging often coincides with metabolic changes, and conserved peptide signaling pathways like the oxytocin/vasopressin system could offer insights into novel therapeutic targets for metabolic disorders and reproductive health.

Researchers investigated the role of the oxytocin/vasopressin-like neuropeptide nematocin in C. elegans aging and reproduction. They genetically manipulated C. elegans to lack signaling from nematocin's two receptors, observing the effects throughout the adult lifespan. Key endpoints included reproductive output (total offspring, egg quality, fertilization success, embryo survival), intestinal fat metabolism, and the regulation of yolk delivery to developing eggs. They also monitored the expression and activity of a fatty-acid desaturase enzyme.

Nematocin signaling was found to restrain reproductive output in C. elegans as animals entered mid-life, with its receptors peaking as reproduction began to wane. Animals genetically lacking nematocin receptor signaling produced more offspring in mid-life. This reproductive benefit stemmed from better egg quality and improved fertilization, rather than enhanced embryo survival. The study revealed that nematocin normally limits the activity of a fatty-acid desaturase enzyme, which is otherwise induced by mating. Furthermore, nematocin actively shapes the amount of yolk delivered to developing eggs. The two nematocin receptors operate via distinct mechanisms:

One receptor specifically tunes intestinal fat metabolism, while the other independently controls yolk delivery to the egg, highlighting a complex, multi-faceted regulatory system.